Proteome analysis of Candida albicans cells undergoing chlamydosporulation

Abstract

Chlamydospore though considered as a unique and rare morphological form of Candida albicans, regulation and significance of chlamydosporulation is not very clear. SWATH-MS analysis of chlamydosporulation specific proteins revealed that 319 (137-Up regulated and 182-Down regulated) proteins expressed differentially. Functional annotation showed significant modulations in proteins involved in cellular architecture (30), carbohydrate (29), amino acid (17), fatty acid (3), Nucleic acid (14), vitamins (1) metabolism as well as signaling (6), stress response (26), transport (cytoplasmic-21, mitochondrial-6 and nuclear-1), gene expression (transcription-12, RNA processing-6, translation-53, PTM-18), proteolysis (15) etc. Enhanced mannan, β1, 3-glucan and chitin contribute in thickening of cell wall while Hyr1 (218-fold) and Als3 (38.16-fold) dominates the cell surface chemistry of chlamydospores. In addition to ergosterol, enhanced sphingolipids, phospholipids and fatty acids make chlamydospore membrane more sturdy and rigid. Up-regulation of maltase (64-fold) followed by enhanced glycolysis and tricarboxylic acid cycle under nutrient-limiting condition is indicative of chlamydosporulation. Glyoxylate and fermentative pathway reported to facilitate survival of C. albicans under glucose limiting and microaerophilic condition was up-regulated. Enhanced biosynthesis of glutathione, trehalose homeostasis, and inhibition of NAD+ generation ,etc., potentiate oxidative, osmotic and nitrosative stress tolerance. Up regulation of Rsr1 (8.83-fold) and down regulation of Bcy1 (4.20-fold), Tfs1 (negative regulator of RAS) indicates cAMP-PKA pathway activates chlamydosporulation through Efg1 (a morphogenic regulator) in our study. In general, morpho-physiological modulations in C. albicans is a result of different sets of transcriptional programs that facilitate survival under nutrient and oxygen limiting condition.